Post-traumatic stress disorder (PTSD) is a major public and VA health concern and exerts substantial burden on as many as 30% (estimates range 14-30%) of veterans returning from deployment in Afghanistan and Iraq from Operations Enduring Freedom, Iraqi Freedom, and New Dawn (OEF/OIF/OND). The past two decades of functional neuroimaging studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have implicated brain dysfunction during cognitive processing in PTSD. However, the limitations of PET and fMRI (high cost, labor and skill intensive, not always tolerated, poor portability) make their translation to clinical application in `real world' settings problematic. Therefore, alternative, `proxy' neuroscience approaches that leverage the existing knowledge about brain function gained from fMRI and PET but that are cost-effective and convenient, and that provide data from larger samples in clinical settings are much needed. Electroencephalography (EEG) measures neurophysiology-based event-related potentials (ERP), is a portable, easy-to-use technique that can be deployed in the `real world' office setting and provides time-locked neural activity measures that have excellent test-retest reliability and temporal resolution. ERPs can track quick and transient cognitive demands and emotionally arousing events. Of the cognitive domains, attention/working memory (WM) dysfunction is a consistently observed and robust impairment in combat PTSD. Moreover, WM can be exacerbated by the interference of emotionally arousing trauma-related ?distractors ? together they are thought to be responsible for the everyday concentration and memory difficulties and re-experiencing and avoidance symptoms of PTSD. Work in our lab and others have shown that ERPs such as the contralateral delay activity (CDA) and late positive potential (LPP) are robust neural indices of visual working memory capacity and emotional arousal, and are altered in depression and anxiety disorders. The extent literature and our Preliminary Data compels us to focus on visual working memory because it has high clinical relevance, is impaired in PTSD and related to PTSD severity, and can be quantified with EEG. It is also important to directly compare PTSD against other internalizing psychopathologies (e.g., Major Depressive Disorder, [MDD], in order to make inferences that cognitive and neurophysiological impairments are specific to PTSD. Using an innovative EEG task ? validated in our laboratory - that dynamically integrates working memory and emotional interference with trauma reminders, the current project proposes to address the following Specific Aims/questions: 1) Do combat veterans with PTSD (compared to those without PTSD) have an attenuated contralateral delay activity (CDA) during visual working memory performance? Does CDA magnitude relate specifically to PTSD symptom severity? [Cognition Alone]; 2) Do combat veterans with PTSD (compared to those without PTSD) have an exaggerated late positive potential (LPP) when processing emotionally arousing trauma reminders? Does LPP magnitude specifically relate to PTSD symptom severity? [Emotion Alone]; 3) Does the intrusion of trauma reminders further impair visual working memory performance and further reduce contralateral delay activity in combat veterans with PTSD (and not in veterans without PTSD)? [Emotion on Cognition Interaction]. Comprehensive psychiatric, neuropsychological testing and EEG- ERP imaging will conducted in three groups (N=60 per group) of OEF/OIF/OND combat veterans (PTSD Group, MDD Group, and Control Group) with similar levels of combat trauma exposure. This design allows for both categorical and continuous analyses in order to link brain function with measures of cognitive function specific to PTSD. The overarching objective is to elucidate precise, brain-based markers and targets of PTSD so that we can improve and expand on therapeutic interventions for our veterans.